ACS Catalysis
Letter
(b) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731−
1770. (c) Marciniec, B. Acc. Chem. Res. 2007, 40, 943−952. (d) Li, C.-
J. Acc. Chem. Res. 2009, 42, 335−344. (e) Colby, D. A.; Bergman, R.
G.; Ellman, J. A. Chem. Rev. 2010, 110, 624−655. (f) Bras, J. L.;
Muzart, J. Chem. Rev. 2011, 111, 1170−1214. (g) Yeung, C. S.; Dong,
V. M. Chem. Rev. 2011, 111, 1215−1292. (h) Liu, C.; Zhang, H.; Shi,
W.; Lei, A. Chem. Rev. 2011, 111, 1780−1824. (i) Ackermann, L.
Chem. Rev. 2011, 111, 1315−1345. (j) Arockiam, P. B.; Bruneau, C.;
Dixneuf, P. H. Chem. Rev. 2012, 112, 5879−5918. (k) Allen, S. E.;
Walvoord, R. R.; Padilla-Salinas, R.; Kozlowski, M. C. Chem. Rev. 2013,
113, 6234−6458. (l) Hartwig, J. F. Acc. Chem. Res. 2014, 45, 864−873.
(m) Ackermann, L. Acc. Chem. Res. 2014, 47, 281−295. (n) Wang, T.;
Jiao, N. Acc. Chem. Res. 2014, 47, 1137−1145.
In summary, we have demonstrated a novel Cu-catalyzed
direct implanting of a benzyl group into simple enones through
nondirected C(sp3)−H activation of toluene. Various α-
substituted enones were efficiently constructed by cleavage of
a C(sp3)−H bond and a C(sp2)−H bond under mild and
neutral reaction conditions. This protocol not only extends the
application of toluenes in synthetic organic chemistry but also
offers an alternative method to prepare α-substituted enones,
which are important structural units in a number of biological
active compounds. The practical advantages of this protocol
include the use of available starting materials (toluenes and
enones) and the avoidance of any preliminary functionalization.
Further investigations to apply this C−H bond activation
strategy to other reactions are in progress.
(6) (a) Qian, B.; Guo, S.; Shao, J.; Zhu, Q.; Yang, L.; Xia, C.; Huang,
H. J. Am. Chem. Soc. 2010, 132, 3650−3651. (b) Xie, P.; Xie, Y.; Qian,
B.; Zhou, H.; Xia, C.; Huang, H. J. Am. Chem. Soc. 2012, 134, 9902−
9905. (c) Xie, Y.; Hu, J.; Wang, Y.; Xia, C.; Huang, H. J. Am. Chem.
Soc. 2012, 134, 20613−20616. (d) Xie, Y.; Hu, J.; Xie, P.; Qian, B.;
Huang, H. J. Am. Chem. Soc. 2013, 135, 18327−18330. (e) Zhang, G.;
Yang, L.; Wang, Y.; Xie, Y.; Huang, H. J. Am. Chem. Soc. 2013, 135,
8850−8853. (f) Xie, P.; Xia, C.; Huang, H. Org. Lett. 2013, 15, 3370−
3373. (g) Qian, B.; Zhang, G.; Ding, Y.; Huang, H. Chem. Commun.
2013, 49, 9839−9841. (h) Zhang, G.; Yu, H.; Qin, G.; Huang, H.
Chem. Commun. 2014, 50, 4331−4334. (i) Han, W.; Zhang, G.; Li, G.;
Huang, H. Org. Lett. 2014, 16, 3532−3535.
ASSOCIATED CONTENT
* Supporting Information
The following files are available free of charge on the ACS
■
S
Experimental details and full spectroscopic data for all
CIF file for C17H16O (CIF)
(7) Vleeschouwer, F. D.; Speybroeck, V. V.; Waroquier, M.;
Geerlings, P.; Proft, F. D. Org. Lett. 2007, 9, 2721−2724.
AUTHOR INFORMATION
Corresponding Author
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(8) For selected examples of transition-metal-catalyzed couplings
with benzyl-radical, see: (a) Lee, J. M.; Park, E. J.; Cho, S. H.; Chang,
S. J. Am. Chem. Soc. 2008, 130, 7824−7825. (b) Xia, Q.; Chen, W.;
Qiu, H. J. Org. Chem. 2011, 76, 7577−7582. (c) Rout, S. K.; Guin, S.;
Ghara, K. K.; Banerjee, A.; Patel, B. K. Org. Lett. 2012, 14, 3982−3985.
(d) Yang, H.; Sun, P.; Zhu, Y.; Yan, H.; Lu, L.; Qu, X.; Li, T.; Mao, J.
Chem. Commun. 2012, 48, 7847−7849. (e) Vanjari, R.; Guntreddi, T.;
Singh, K. N. Org. Lett. 2013, 15, 4908−4911. (f) Shu, Z.; Ye, Y.; Deng,
Y.; Zhang, Y.; Wang, J. Angew. Chem., Int. Ed. 2013, 52, 10573−10576.
(g) Zhou, S.-L.; Guo, L.-N.; Wang, H.; Duan, X.-H. Chem. - Eur. J.
2013, 19, 12970−12973. (h) Zhou, S.-L.; Guo, L.-N.; Duan, X.-H. Eur.
J. Org. Chem. 2014, 8094−8100. (i) Zhou, S.-L.; Guo, L.-N.; Wang, S.;
Duan, X.-H. Chem. Commun. 2014, 50, 3589−3591.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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This research was supported by the Chinese Academy of
Sciences and the National Natural Science Foundation of China
(21222203, 21372231, and 21133011).
REFERENCES
■
(9) CCDC 1041682 contains the supplementary crystallographic
data for this paper. This data can be obtained free of charge from The
(10) Zanello, P.; Leoni, P. Can. J. Chem. 1985, 63, 922−927.
(11) (a) Khursan, S. L.; Mikhailov, D. A.; Yanborisov, V. M.; Borisov,
D. I. React. Kinet. Catal. Lett. 1997, 61, 91−95. (b) Alnajjar, M. S.;
Zhang, X.-M.; Gleicher, G. J.; Truksa, S. V.; Franz, J. A. J. Org. Chem.
2002, 67, 9016−9022.
(1) (a) Koltunov, K. Y.; Walspurger, S.; Sommer, J. Tetrahedron Lett.
2005, 46, 8391−8394. (b) Reynolds, T. E.; Scheidt, K. A. Angew.
Chem., Int. Ed. 2007, 46, 7806−7809. (c) Saito, A.; Umakoshi, M.;
Yagyu, N.; Hanzawa, Y. Org. Lett. 2008, 10, 1783−1785. (d) Wang, J.;
Wang, X.; Ge, Z.; Cheng, T.; Li, R. Chem. Commun. 2010, 46, 1751−
1753. (e) Liu, Y.; Zhu, J.; Qian, J.; Jiang, B.; Xu, Z. J. Org. Chem. 2011,
76, 9096−9101. (f) Ma, S.; Wu, L.; Liu, M.; Wang, Y. Org. Biomol.
Chem. 2012, 10, 3721−3729.
(2) (a) Shimazaki, A.; Suhara, H.; Ichikawa, M.; Matsugi, T.; Konomi,
K.; Takagi, Y.; Hara, H.; Rao, P. V.; Epstein, D. L. Biol. Pharm. Bull.
2004, 27, 846−850. (b) Sahu, N. K.; Balbhadra, S. S.; Choudhary, J.;
Kohli, D. V. Curr. Med. Chem. 2012, 19, 209−225.
(3) (a) Dams, M.; Vos, D. E. D.; Celen, S.; Jacobs, P. A. Angew.
Chem., Int. Ed. 2003, 42, 3512−3515. (b) Hong, Y.-T.; Barchuk, A.;
Krische, M. J. Angew. Chem., Int. Ed. 2006, 45, 6885−6888. (c) Dai, L.-
Z.; Qi, M.-J.; Shi, Y.-L.; Liu, X.-G.; Shi, M. Org. Lett. 2007, 9, 3191−
3194. (d) Yu, M.; Li, G.; Wang, S.; Zhang, L. Adv. Synth. Catal. 2007,
349, 871−875. (e) Egi, M.; Umemura, M.; Kawai, T.; Akai, S. Angew.
Chem., Int. Ed. 2011, 50, 12197−12200. (f) AntiÇolo, A.; Carrillo-
Hermo-silla, F.; Cadierno, V.; Garcia-Alvarez, J.; Otero, A.
ChemCatChem 2012, 4, 123−128. (g) Schranck, J.; Wu, X.-F.;
Neumann, H.; Beller, M. Chem.Eur. J. 2012, 18, 4827−4831.
(h) Martínez, A.; Zumbansen, K.; Dohring, A.; Gemmeren, M. V.; List,
̈
B. Synlett 2014, 25, 932−934.
(4) For selected reviews on the Morita−Baylis−Hillman reaction,
see: (a) Basaviah, D.; Rao, A. J.; Satyanarayana, T. Chem. Rev. 2003,
103, 811−892. (b) Wei, Y.; Shi, M. Chem. Rev. 2013, 113, 6659−6690.
(5) For selected recent reviews on CDC reactions, see:
(a) Braunstein, P.; Morise, X. Chem. Rev. 2000, 100, 3541−3552.
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